Indeed, the senescence of the vascular endothelium and the degeneration of the tissues subjected to inflammatory processes are accelerated by repeated or chronic inflammation of the vascular endothelium.
Cell senescence is a phenomenon resulting in an increase in the volume of the cell, a decrease in or loss of the normal capacity of the cell to divide, a decrease in its regenerative and metabolic functions, and an increase in the activity of cellular degradative enzymes. All these changes characterize the senescent phenotype.
This senescent phenotype has been observed in young cells subjected to repeated stress due to inflammatory reactions.
The initial phase of inflammation occurs at the blood/tissue interface and consists in the recruitment of immunologically competent cells, in particular activated leucocytes. Inflammation consists in targeting and killing infectious microorganisms and other pathogens. The immunologically competent cells capable of acting against these microorganisms circulate in blood and must therefore enter the tissues to carry out their role; to do this, they must cross the barrier formed by the vascular wall. They do this by being recruited by the vascular endothelial cells lining the vessels and which transfer them into the underlying tissue. Vascular endothelial cells are activated by specific signals from infected or injured tissue, or directly by the immunologically competent cells, and this activation results in the effect of a significant increase of their recruitment ability. The state of activation of vascular endothelial cells can be measured by the appearance of specific markers. In particular, the expression level of adhesion molecules such as ICAM-1 (INTER-CELLULAR ADHESION MOLECULE-1) allows the degree of vascular endothelial cells activation leading to the recruitment of immunologically competent cells to be assessed.
Another consequence of inflammatory stress is the rearrangement of the actin cytoskeleton in activated vascular endothelial cells. Inflammatory stress results in the formation of polymerised actin fibres (so-called “stress” fibres) that can be revealed by rhodamine-conjugated phalloidin staining.
Under normal circumstances, in a primary cell culture of vascular endothelial cells, the activation due to an inflammatory state of the cells is reversible. During senescence, cells gradually lose this reversibility and thus permanently express adhesion molecules, even in the absence of an external stimulation. There are two consequences for this loss of reversibility: firstly, the constant recruitment of immunologically competent cells is an additional source of inflammatory stress for tissues; and secondly, because of this, vascular endothelial cells are more available to recruit tumour metastases which use the same adhesion molecules to invade tissues.